Cancer is a leading cause of death worldwide: it accounted for 7.4 million deaths (around 13% of all deaths) in 2004. Deaths from cancer worldwide are projected to continue rising, with an estimated 12 million deaths in 2030.
Because cancer is a genetic disease, molecular changes, such as genetic and epigenetic DNA modifications, which result in neoplastic transformation, can be used as markers for the early detection of cancer.
Colorectal Cancer
Despite improvements in screening, colorectal cancer (CRC) remains the second leading cause of cancer death in the United States. When CRC is detected in its earliest stages, the survival rate can be as high as 90% compared with a survival rate of approximately 10% once the cancer has distantly metastasized. Currently, the recommended screening tests for CRC are colonoscopy or flexible sigmoidoscopy, but the adherence rate to take these tests is low (40%) in adults in the United States due to inconvenience, fear of discomfort, and the risks involved in invasive screening tests. The noninvasive fecal occult blood test (FOBT) is also available, but its sensitivity is low (30%). Another emerging noninvasive screening test for CRC is the stool genetic test. Although a high specificity (92%) was obtained in a well-defined screening study in an average-risk population, the sensitivity (52%) has not been satisfactory. Thus, U.S. Health Care authorities continue to recommend an invasive flexible sigmoidoscopy or colonoscopy every 10 years for average-risk adults despite the high cost and invasive nature of these tests.
Hepatocellular Carcinoma
Hepatocellular carcinoma (HCC) is the fifth most frequent cancer in the world, and is the third leading cause of cancer mortality, responsible for between 250,000 and 800,000 deaths per year. HCC is an aggressive malignancy with a poor prognosis with the 5 year survival rates are usually less than 5% following diagnosis using conventional methods of detection and treatment. However, early surgical and chemotherapeutic intervention can improve the prognosis, if early detection is possible. Unfortunately, the early stage of liver cancer is mostly asymptomatic, making the early detection of liver cancer a challenge. Current methods in detecting HCC include monitoring high risk groups such as those infected with HBV or HCV with regular (usually annual or biannual) physical assessments, serum liver function tests (LFTs), or ultrasound imaging for the detection of small masses in the liver. Ultrasound imaging is very expensive, making its routine use prohibitive. Moreover, detection requires the appearance of masses of at least 3 cm in size, and the outcome of the prognosis at that size is very poor. In addition to imaging techniques, the detection of the elevated serum concentrations of alpha-feto protein (AFP) has provided a useful surrogate marker for disease with at least 60% of the cases of HCC having the elevated AFP level at the time of diagnosis. However, the elevated level of AFP is influenced by and can occur because of a number of other non-malignant physiological events. It is nearly impossible to detect HCC early using current methods of detection. Thus, there is a clear and urgent need for non-invasive, reliable methods for the early detection of HCC.
Success in the treatment of individuals with cancer, such as CRC or HCC, often depends upon early detection. The earlier a tumor is detected, the better the prognosis. Many of the 520,000 lives lost to cancer each year could be saved with early detection. In many pre-neoplastic conditions, such as an inherited predisposition to a specific tumor type or in a disease-promoting neoplastic transformation, high risk individuals could be identified, and early detection programs could be implemented. From the patient's point of view, a diagnostic test is less unpleasant, invasive, and expensive, and is also more likely to be used. The importance of a non-invasive diagnosis for early cancer detection can be illustrated by the colorectal cancer screening test. These tests such as rectocolonoscopy and sigmoidoscopy are effective in detecting CRC early. Unfortunately, the low compliance rate (25-35%) of adults in the US has been a problem due to inconvenience, fear of discomfort, and the risk involved in the screening test. Thus, a noninvasive, effective screening method is needed to improve a patient's comfort, so that the compliance rate can be increased, and cancer can be detected early. In all, more work is needed to develop a noninvasive, less unpleasant, highly sensitive, and less expensive screening test to augment adherence rates and to increase the role of early detection in disease prognosis.